title: Inhibitory effects of propofol on intracellular signaling by endothelin-1 in aortic smooth muscle cells.
abstract: BACKGROUND
  Blood pressure decreases when propofol is administered. However, the exact mechanism underlying the vascular effects of propofol has not yet been elucidated. Endothelin produced by vascular endothelial cells is a potent vasoactive peptide that elicits prolonged contraction of vascular smooth muscle cells. The effects of propofol on endothelin-1-induced intracellular signaling in an aortic smooth muscle cell line, A10 cells, were examined.
  
  
  METHODS
  Cultured A10 cells were pretreated with propofol for 20 min and then stimulated with endothelin-1. The effect of propofol on the endothelin-1-induced Ca2+ influx into A10 cells was evaluated by measuring intracellular 45Ca2+. The effects of propofol on the endothelin-1-induced activation of phosphatidylinositol-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D were evaluated by measuring the formation of inositol phosphates and choline, respectively. The effect of propofol on endothelin-1 binding to its receptor was determined by an [125I] endothelin-1-binding assay.
  
  
  RESULTS
  Propofol inhibited the endothelin-1-induced Ca2+ influx, but this was significant only at supuraclinical concentrations. The endothelin-1-stimulated formation of inositol phosphates was significantly suppressed by propofol. However, propofol had no effect on the formation of inositol phosphates induced by NaF, an activator of heterotrimeric guanosine triphosphate (GTP)-binding proteins. Propofol inhibited the endothelin-1-induced formation of choline. Propofol had no effect on the binding of endothelin-1 to its receptor.
  
  
  CONCLUSIONS
  These results suggest that propofol inhibits endothelin-1-induced intracellular signaling in vascular smooth muscle cells. The inhibitory effect of propofol might be exerted at a point between the endothelin-1 receptor and its GTP-binding protein. However, because all significant effects are observed at high concentrations, clinical relevance is unclear.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanabe
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
authors.forename: T
authors.initials: T
authors.lastname: Kaida
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
authors.forename: M
authors.initials: M
authors.lastname: Niwa
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Dohi
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D019332:Endothelin-1; D007295:Inositol Phosphates; D011493:Protein Kinase C; D002118:Calcium; D015742:Propofol